Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-05-18 DOI:10.1038/s41467-025-59626-0

Gregory J. Golden, Vincent H. Wu, Jacob T. Hamilton, Kevin R. Amses, Melanie R. Shapiro, Alberto Sada Japp, Chengyang Liu, M. Betina Pampena, Leticia Kuri-Cervantes, James J. Knox, Jay S. Gardner, Mark A. Atkinson, Todd M. Brusko, Eline T. Luning Prak, Klaus H. Kaestner, Ali Naji, Michael R. Betts

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Abstract

Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. However, characterization of the immunological processes occurring in human pancreatic lymphatic tissues is lacking. Here, we conduct a comprehensive study of immune cells from pancreatic, mesenteric, and splenic lymphatic tissues of non-diabetic control (ND), β cell autoantibody-positive non-diabetic (AAb+), and T1D donors using flow cytometry and CITEseq. Compared to ND pancreas-draining lymph nodes (pLN), AAb+ and T1D donor pLNs display decreased CD4+ Treg and increased stem-like CD8+ T cell signatures, while only T1D donor pLNs exhibit naive T cell and NK cell differentiation. Mesenteric LNs have modulations only in CD4+ Tregs and naive cells, while splenocytes lack these perturbations. Further, T cell expression of activation markers and IL7 receptor correlate with T1D genetic risk. These results demonstrate tissue-restricted immune changes occur before and after T1D onset.

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1型糖尿病发病前后人胰腺淋巴组织的免疫扰动

胰腺β细胞的自身免疫破坏导致1型糖尿病（T1D），胰腺免疫浸润是这一过程的一个关键特征。然而，在人类胰腺淋巴组织中发生的免疫过程的表征是缺乏的。在这里，我们使用流式细胞术和CITEseq对来自非糖尿病对照（ND）、β细胞自身抗体阳性的非糖尿病（AAb+）和T1D供者的胰腺、肠系膜和脾淋巴组织的免疫细胞进行了全面研究。与ND胰腺引流淋巴结（pLN）相比，AAb+和T1D供体pLN显示CD4+ Treg减少，干细胞样CD8+ T细胞特征增加，而只有T1D供体pLN表现出幼稚T细胞和NK细胞分化。肠系膜ln仅在CD4+ treg和幼稚细胞中有调节，而脾细胞没有这些扰动。此外，T细胞活化标记物和IL7受体的表达与T1D遗传风险相关。这些结果表明，组织限制性免疫变化发生在T1D发病前后。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.